The extracellular matrix of the lung and airway responsiveness in asthma.

Abstract The extracellular matrix is the main determinant of the structure and of mechanical behaviour of the lung. The extracellular matrix is also responsible for the mechanical interdependence between airway and parenchyma due to the alveolar attachments to the airways. Asthma is characterized by bronchial hyperresponsiveness, airway remodelling and inflammation, and an altered extracellular matrix may play a role in all these functional and structural abnormalities. The excessive airway narrowing observed in asthma may be related to the altered viscoelastic properties of lung parenchyma and airway wall, determining a decrease in the mechanical load opposing the airways' smooth muscle contraction. Indeed, an altered extracellular matrix deposition in asthma in humans, has been demonstrated. In addition, in the asthmatic lung, the matrix seems to contribute to airway inflammation, airway remodelling, and to those alterations of the smooth muscle function of the airway and morphology typical of asthma

Sputum induced cellularity in a group of traffic policemen.

It has been demonstrated that a group of workers (e.g. waste handlers) daily exposed to a traffic related air pollution present airway inflammation in term of an increase of neutrophilic inflammation. The aim of our study was to determine the presence of airways inflammation detected by induced sputum in a population of traffic policemen (TP) in the city of Bari, compared to a group of healthy subjects (HS) without any occupational exposure to inhalation of traffic-related air pollution. Twelve non smokers, non atopics, healthy traffic policemen with a history of exposure to airway pollution and 12 HS underwent sputum induction. TP show a statistically significant increase in the percentage neutrophil cell count (median and IQ range) compared to the HS (65 and 13.5 vs. 40.5 and 9.5; p<0.01). In conclusion we have found that policemen chronically exposed to air pollution presented airway neutrophilic inflammation and the results of this pilot study could be strictly considered for the long term effect of a traffic pollution in airway inflammation and the lung function

Exhaled Interleukine-6 and 8-isoprostane in chronic obstructive pulmonary disease: effect of carbocysteine lysine salt monohydrate (SCMC-Lys).

Chronic obstructive pulmonary disease (COPD) is characterized by an airways inflammation and by an enhanced generation of reactive oxygen species. The aim of our study was to assess the inflammation and the oxidative stress in airways of COPD patients with acute exacerbation of disease and in stability. Furthermore, we investigated the anti-inflammatory and antioxidant effects of 6 months treatment with carbocysteine lysine salt monohydrate (SCMC-Lys) in COPD. We studied 30 mild acute COPD, 10 mild stable COPD and 15 healthy subjects. 8-isoprostane and Interleukine-6 were measured in their breath condensate through immunoassay. Significantly higher concentrations of exhaled 8-isoprostane and Interleukine-6 were found in acute COPD patients compared to stable COPD and healthy controls (21.8+/-5.1 vs. 13.2+/-2.0 vs. 4.7+/-1.8 pg/ml and 7.4+/-0.9 vs. 5.8+/-0.2 vs. 2.7+/-0.6 pg/ml, p<0.0001). COPD patients treated with SCMC-Lys showed a marked reduction of exhaled 8-isoprostane and Interleukine-6 (8.9+/-1.5 and 4.6+/-0.8 pg/ml, p<0.0001). These findings suggest that there is an increase of 8-isoprostane and Interleukine-6 concentrations in the breath condensate of COPD patients compared to healthy controls especially during acute exacerbations of the disease. Moreover, we showed an anti-inflammatory and antioxidant effect of short-term administration of SCMC-Lys in COPD, suggesting the importance of a further placebo-controlled study that should evaluate the effects of this drug

Validity and reproducibility of morphologic analysis of nasal secretions obtained using ultrasonic nebulization of hypertonic solution.

BACKGROUND: Collection of nasal secretions is important for the evaluation of upper airways inflammation in many nasal disorders. OBJECTIVE: To study the validity and reproducibility of nasal secretion cellularity induced by nebulization of hypertonic solution in patients with allergic rhinitis (AR), patients with nonallergic rhinitis with eosinophilia syndrome (NARES), and control subjects. METHODS: Sixty-eight individuals (29 with AR [mean +/- SD age, 33.3 +/- 16.9 years], 23 with NARES [mean +/- SD age, 46.4 +/- 16.6 years], and 16 controls [mean +/- SD age, 42.1 +/- 15.1 years]) underwent ultrasonic nebulization of hypertonic (4.5%) saline solution on 2 different occasions to study the validity and reproducibility of total and differential cell counts of nasal secretions. RESULTS: The mean +/- SD percentage of eosinophils was significantly higher in samples from patients with AR (20.8% +/- 23.1%) and NARES (18.7% +/- 22.8%) than in samples from controls (0.6% +/- 0.6%; P < .001 for both). There was a significant correlation between 2 samples of nasal secretions obtained on 2 different occasions for percentages of macrophages, neutrophils, eosinophils, and epithelial cells. CONCLUSIONS: The analysis of nasal secretions obtained using ultrasonic nebulization of hypertonic solution can distinguish patients with AR and NARES from controls. The reproducibility of this technique is good for macrophages, neutrophils, eosinophils, and epithelial cells. This method could be used to detect nasal airway inflammation in clinical settings

A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1], the case-fatality ratio of measles [2], and the probability of infection and, given infection, of symptoms in cholera [3]. Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4]. These distributions can be distinguished in vaccine field trials from the time dependence of infections [5]. Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6], [7], although the results are not comparable across regions unless there is explicit control for baseline transmission [8]. Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9]–[11] and natural settings [12], [13]. These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health

Città della Conciliazione, Grugliasco, Torino, Italy, 2005-2009

Pubblicazione del progetto Città Universitaria della Conciliazione a Grugliasco (TO) nel numero della rivista World Architecture dedicato ai progetti della Città di Torin

Correction: optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging

Abstract Background Stem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate in vivo. Non-invasive cell tracking can provide knowledge about mechanisms responsible for functional improvement of host tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label and visualize various cell types with magnetic resonance imaging (MRI). In this study we performed experiments designed to investigate the biological properties, including proliferation, viability and differentiation capacity of mesenchymal cells (MSCs) labeled with clinically approved SPIONs. Results Rat and mouse MSCs were isolated, cultured, and incubated with dextran-covered SPIONs (ferumoxide) alone or with poly-L-lysine (PLL) or protamine chlorhydrate for 4 or 24 hrs. Labeling efficiency was evaluated by dextran immunocytochemistry and MRI. Cell proliferation and viability were evaluated in vitro with Ki67 immunocytochemistry and live/dead assays. Ferumoxide-labeled MSCs could be induced to differentiate to adipocytes, osteocytes and chondrocytes. We analyzed ferumoxide retention in MSCs with or without mitomycin C pretreatment. Approximately 95% MSCs were labeled when incubated with ferumoxide for 4 or 24 hrs in the presence of PLL or protamine, whereas labeling of MSCs incubated with ferumoxide alone was poor. Proliferative capacity was maintained in MSCs incubated with ferumoxide and PLL for 4 hrs, however, after 24 hrs it was reduced. MSCs incubated with ferumoxide and protamine were efficiently visualized by MRI; they maintained proliferation and viability for up to 7 days and remained competent to differentiate. After 21 days MSCs pretreated with mitomycin C still showed a large number of ferumoxide-labeled cells. Conclusions The efficient and long lasting uptake and retention of SPIONs by MSCs using a protocol employing ferumoxide and protamine may be applicable to patients, since both ferumoxides and protamine are approved for human use.</p

Técnicas continuas de depuración extrarrenal. ¿Precoces o tardías? ¿Cuál es el momento idóneo para su inicio?

The development of acute kidney injury (AKI) is a frequent problem in critical care units (ICUs), specifically in subpopulations admitted with a diagnosis of sepsis or septic shock. In the literature, the indications for the application of CRRT are clear (both of renal and extrarenal origin). However, it seems unclear in any previously published study the ideal time of the beginning of these techniques, nor the impact this has on morbidity and mortality. The objective of this clinical trial is to analyze whether there are differences in mortality between 2 patients groups with AKI and septic shock, depending on the early or late onset of CRRT. It is open (no masking), and may fall into measurement bias during the measurement of the data. The study groups were homogeneous and randomized. However, they do not specify the type of CRRT mode used. The sample size initially calculated according to the power conferred on the study was not finally reached. The measurements were objective. Nonetheless, they do not clarify why they designate the early CRRT as early in the first 12 hours after the development of AKI and late 48 hours later. Results: There are no mortality differences at 90 days (P = 0.38, not significant). It seems that in the late group 38% did not receive CRRT, and 17% received it early. The late group presented significantly fewer days with CRRT. There were no differences in days of mechanical ventilation, vasopressors or ICU stay.El desarrollo de insuficiencia renal aguda (IRA) constituye una problemática frecuente en las unidades de cuidados críticos (UCI), concretamente en las subpoblaciones ingresadas con diagnóstico de sepsis o shock séptico. En la literatura, las indicaciones de aplicación de TCRR están claras (tanto de origen renal como extrarrenal). Sin embargo, no parece claro en ningún estudio publicado previamente el momento ideal del inicio de dichas técnicas, ni la repercusión que esto tiene en la morbimortalidad. El objetivo de este ensayo clínico es analizar si existen diferencias en la mortalidad entre 2 grupos de pacientes con lesión renal aguda y shock séptico, según el inicio precoz o tardío de las TCRR. Es abierto (no hay enmascaramiento), pudiendo caer en sesgo de medición durante la medición de los datos. Los grupos de estudio fueron homogéneos, con aleatorización al azar. Sin embargo, no especifican el tipo de modalidad de TCRR utilizada. El tamaño muestral calculado inicialmente según la potencia conferida al estudio no fue alcanzado finalmente. Las mediciones fueron objetivas. Sin embargo, no aclaran por qué designan como precoz al inicio de las TCRR en las primeras 12 horas desde el desarrollo de LRA y tardío a 48 horas después. Resultados: No hay diferencias de mortalidad a los 90 días (P=0.38, no significativo). Sin embargo, en el grupo tardío un 38% no recibieron TCRR, y 17 % lo recibieron precozmente. El grupo tardío presentó de forma significativa menos días con TCRR. No hubo diferencias en días de ventilación mecánica, vasopresores ni estancia en UCI

Experimental Quantum Hamiltonian Learning

Efficiently characterising quantum systems, verifying operations of quantum devices and validating underpinning physical models, are central challenges for the development of quantum technologies and for our continued understanding of foundational physics. Machine-learning enhanced by quantum simulators has been proposed as a route to improve the computational cost of performing these studies. Here we interface two different quantum systems through a classical channel - a silicon-photonics quantum simulator and an electron spin in a diamond nitrogen-vacancy centre - and use the former to learn the latter's Hamiltonian via Bayesian inference. We learn the salient Hamiltonian parameter with an uncertainty of approximately $10^{-5}$. Furthermore, an observed saturation in the learning algorithm suggests deficiencies in the underlying Hamiltonian model, which we exploit to further improve the model itself. We go on to implement an interactive version of the protocol and experimentally show its ability to characterise the operation of the quantum photonic device. This work demonstrates powerful new quantum-enhanced techniques for investigating foundational physical models and characterising quantum technologies